title: Effects of morphine on pain-elicited and pain-suppressed behavior in CB1 knockout and wildtype mice.
abstract: BACKGROUND
  Pharmacological manipulations of the type 1 cannabinoid receptor (CB1) suggest a role for CB1 in morphine-induced antinociception, but studies utilizing CB1 knockout (KO) mice do not support this conclusion. Since studies using CB1 KO mice to study morphine's antinociceptive effects have only examined thermal nociception, this study examines these interactions in models that employ a chemical stimulus.
  
  
  OBJECTIVE
  To determine whether the findings obtained with thermal pain models extend to other models, the effects of morphine on acetic acid-induced writhing were examined in CB1 KO and wildtype (WT) mice. Behaviors that decrease in response to acid injection, feeding and wheel running, were also examined, and investigations were carried out in the thermal hotplate assay. The CB1 antagonist SR141716A was also examined in these assays.
  
  
  RESULTS
  Morphine completely blocked acid-induced writhing (1.0-10.0 mg/kg) and increased response latencies in the hotplate (10.0-32.0 mg/kg) in both genotypes. Morphine (3.2 mg/kg) significantly attenuated the suppression of wheel running but did not completely prevent this effect in either genotype. Morphine did not alter pain-suppressed feeding. In each of these assays, morphine's effects were not altered in CB1 KO mice compared with WT mice; however, SR141716A attenuated morphine's effects in C57BL/6 mice.
  
  
  CONCLUSIONS
  The effects of morphine do not differ in CB1 KO and WT mice in preclinical pain models using thermal and chemical stimuli. Since SR141716A did attenuate the effects of morphine, it is possible that CB1 KO mice undergo developmental changes that mask the role of CB1 receptors in morphine's antinociceptive effects.
authors.affiliation: Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. MILLERLL@email.unc.edu
authors.forename: Laurence L
authors.initials: LL
authors.lastname: Miller
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Picker
authors.forename: Karl T
authors.initials: KT
authors.lastname: Schmidt
authors.forename: Linda A
authors.initials: LA
authors.lastname: Dykstra
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D000077285:Rimonabant
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D009020:Morphine; D000077285:Rimonabant